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Search Results (318)

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Keywords = Solid lipid nanoparticles (SLNs)

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44 pages, 811 KB  
Review
Lipid-Based Drug Delivery Systems as Emerging Tools to Overcome Antifungal Resistance
by Lide Arana, Andrea Guridi, Elena Sevillano, Esther Tamayo, Elena Eraso, Itziar Alkorta and Ianire Mate
Int. J. Mol. Sci. 2026, 27(10), 4487; https://doi.org/10.3390/ijms27104487 - 16 May 2026
Viewed by 358
Abstract
Fungal infections represent an escalating global health challenge due to their increasing incidence, the emergence of multidrug-resistant pathogens, and the limited development of new antifungal agents. Therapeutic efficacy is compromised by mutations in drug targets, overexpression of efflux pumps, alterations in the ergosterol [...] Read more.
Fungal infections represent an escalating global health challenge due to their increasing incidence, the emergence of multidrug-resistant pathogens, and the limited development of new antifungal agents. Therapeutic efficacy is compromised by mutations in drug targets, overexpression of efflux pumps, alterations in the ergosterol biosynthetic pathway, biofilm-associated tolerance, and extensive genomic plasticity. The growing prevalence of antifungal resistance and the limited availability of effective therapeutic options highlight the urgent need to strengthen epidemiological surveillance and accelerate research into innovative therapeutic strategies. In this review, we discuss the potential of lipid-based drug delivery systems (LDDSs) as a versatile strategy to optimize antifungal administration and overcome resistance mechanisms. Liposomes (LPs), solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and lipid nanoparticles (LNPs) offer high biocompatibility, efficient encapsulation of hydrophobic compounds, structural stability, and controlled drug release. Their nanoscale properties facilitate penetration into biofilms, promote intracellular uptake, and reduce the impact of efflux-mediated drug extrusion, thereby improving cellular penetration and circumventing resistance pathways. In addition, LDDSs increase bioavailability, reduce toxicity, and promote drug accumulation within poorly accessible tissue compartments. Overall, LDDSs represent a promising approach to expand the therapeutic arsenal against both superficial and invasive fungal infections, particularly those caused by multidrug-resistant pathogens. Full article
(This article belongs to the Special Issue Molecular Advances in Antimicrobial Nanoparticles)
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16 pages, 1505 KB  
Article
Meroterpenoids and Fucoxanthin from the Brown Seaweed Sargassum incisifolium: Solid Lipid Nanoparticle Delivery, Physicochemical Characterization, and Antimicrobial Activity
by Witness Sibiya, Mogammad L. Samsodien, Jo-Marie Vreulink, Marilize Le Roes-Hill, John J. Bolton, Denzil R. Beukes and Edith Antunes
Molecules 2026, 31(10), 1646; https://doi.org/10.3390/molecules31101646 - 13 May 2026
Viewed by 131
Abstract
Marine macroalgae are a rich source of bioactive natural products, although the application of many lipophilic compounds is limited by poor aqueous solubility and instability. This study investigated metabolites isolated from the South African brown seaweed Sargassum incisifolium and evaluated a solid lipid [...] Read more.
Marine macroalgae are a rich source of bioactive natural products, although the application of many lipophilic compounds is limited by poor aqueous solubility and instability. This study investigated metabolites isolated from the South African brown seaweed Sargassum incisifolium and evaluated a solid lipid nanoparticle (SLN) system to improve their physicochemical properties and enable bioactivity studies. Five metabolites, including one previously unreported derivative and four known metabolites (including fucoxanthin), were isolated and characterized using standard chromatographic and spectroscopic techniques. SLNs composed of stearic acid and Poloxamer 188 were prepared via hot homogenization and characterized using dynamic light scattering, scanning electron microscopy, thermogravimetric analysis, and NMR, which confirmed the efficient encapsulation of the lipophilic compounds. Antimicrobial activity against clinically relevant bacterial and fungal pathogens was evaluated using a resazurin-based microdilution assay, with results expressed as percentage growth relative to untreated controls. The pure compounds exhibited moderate, concentration-dependent activity, while the SLN formulations improved dispersibility, and in several cases, reduced % growth or produced more consistent responses, particularly against Gram-positive bacteria and Candida auris. Although activity remained lower than that of conventional antimicrobials, these findings demonstrate that SLN-based delivery enables functional evaluation of hydrophobic marine metabolites and supports further development of Sargassum-derived natural products. Full article
(This article belongs to the Special Issue Natural Products and Microbiology in Human Health, 2nd Edition)
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48 pages, 3877 KB  
Review
Nanoparticles in Therapy and Diagnosis: A Comprehensive Review of Mechanisms, Applications, and Translational Challenges
by Pooja Tiwary, Krishil Oswal, Ryan Varghese and Pardeep Gupta
J. Nanotheranostics 2026, 7(2), 11; https://doi.org/10.3390/jnt7020011 - 7 May 2026
Viewed by 606
Abstract
Background: Conventional therapeutic and diagnostic approaches, despite improving clinical outcomes, remain limited by poor bioavailability, inadequate targeting, suboptimal pharmacokinetics, and systemic toxicity, particularly in complex diseases. To overcome this, nanomedicine has emerged as a transformative strategy, employing engineered nanoparticles to enhance drug stability, [...] Read more.
Background: Conventional therapeutic and diagnostic approaches, despite improving clinical outcomes, remain limited by poor bioavailability, inadequate targeting, suboptimal pharmacokinetics, and systemic toxicity, particularly in complex diseases. To overcome this, nanomedicine has emerged as a transformative strategy, employing engineered nanoparticles to enhance drug stability, controlled release, targeted delivery, and diagnostic performance, thereby enabling theranostic applications. This review evaluates major nanoparticle platforms in therapy and diagnosis, comparing their mechanisms, applications, and challenges while highlighting their potential to advance precision medicine and theranostic strategies. Method: For providing the context and evidence, relevant literatures were sourced from Google Scholar, PubMed, and ScienceDirect using targeted keywords including “drug delivery,” “diagnostics,” “nanoparticles,” “nanomedicine,” “nano drug delivery,” “nanotheranostics,” “targeted therapy,” “controlled drug release,” “solid lipid nanoparticles (SLNs),” “lipid nano carriers (LNCs),” and “inorganic nanoparticles.” Although no strict time limit was applied during the literature search, clinical trial data were collected and analyzed up to January 2026. Given that clinical trial registries are continuously updated, the included trials represent the status at the time of data retrieval. However, it is pertinent to note that the earliest relevant studies appeared in 1973. Conclusions: This review highlights nanoparticle fundamentals, major material classes, mechanisms of action, and applications in targeted therapy, imaging, and theranostics. It also addresses translational barriers related to safety, scalability, biological complexity, and regulatory compliance. Overcoming these challenges through standardized characterization and interdisciplinary collaboration is crucial for clinical adoption. Future efforts should focus on AI-driven design, computational tools, smart nanomedicines, and advanced biosensing technologies to integrate nanoparticle-enabled precision diagnostics and therapy into routine clinical practice. Full article
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13 pages, 2521 KB  
Article
Assessing the Impact on Barrier Function of Black Soldier Fly Larvae Lipids-Based Nanoparticles
by Cíntia Almeida, Margarida Gingado, Carolina Santos, Carla Turiel, Thalita Cândido, Ana Júlio, Catarina Pereira-Leite and Catarina Rosado
Cosmetics 2026, 13(3), 112; https://doi.org/10.3390/cosmetics13030112 - 5 May 2026
Viewed by 317
Abstract
Epidermal barrier dysfunction, driven by disorganization and altered composition of the stratum corneum (SC) lipid matrix, underlies multiple inflammatory dermatoses, namely atopic dermatitis (AD). The lipid fraction derived from Black Soldier Fly larvae (BSFL) biomass has emerged as a promising biomaterial for skin [...] Read more.
Epidermal barrier dysfunction, driven by disorganization and altered composition of the stratum corneum (SC) lipid matrix, underlies multiple inflammatory dermatoses, namely atopic dermatitis (AD). The lipid fraction derived from Black Soldier Fly larvae (BSFL) biomass has emerged as a promising biomaterial for skin health applications, particularly for restoring barrier function. Following previous work on the development of solid lipid nanoparticles (SLNs) incorporating BSFL lipid extract, the present study focused on the mechanistic evaluation of the occlusive, moisturizing and skin reinforcement potential of these nanoformulations (NFs), by exploring both in vitro and in vivo models. The compatibility assays showed no adverse effects after patch testing on healthy or atopic individuals, nor alterations on skin hydration, transepidermal water loss (TEWL), or redness. In vitro studies confirmed the ability of these NFs to form an occlusive lipid film, hampering moisture loss, with 39% reduction of water loss compared to the control. Efficacy assays in human volunteers revealed a statistically significant improvement in epidermal conditions at treated sites, evidenced by enhanced SC hydration. The plastic occlusion stress test (POST) revealed a trend toward a reduced evaporation half-life, suggesting a modulation of the epidermal water dynamics, although the effect did not reach statistical significance. Overall, BSFL-based lipid nanoparticles emerge as emollient agents with broad potential for incorporation into next-generation cosmetic and pharmaceutical products for the management of AD. Full article
(This article belongs to the Special Issue Feature Papers in Cosmetics in 2026)
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40 pages, 2001 KB  
Review
Botanical and Upcycled Bioactives for Advanced Topical Formulations: Mechanistic Pathways, Cutaneous Delivery, and Sustainability-by-Design
by Salvatore Panza, Beatrice Pellegrini, Dorotea Fiore, Martine Tarsitano, Antonia Mancuso, Maria Chiara Cristiano and Donatella Paolino
Pharmaceutics 2026, 18(3), 375; https://doi.org/10.3390/pharmaceutics18030375 - 18 Mar 2026
Viewed by 929
Abstract
Natural and sustainable cosmetics represent a rapidly evolving frontier in dermatological science, integrating plant-derived bioactive compounds with advanced delivery technologies and environmentally conscious formulation design. Botanical ingredients, including polyphenols, flavonoids, terpenoids, alkaloids, and polysaccharides, modulate key biological pathways involved in oxidative stress, inflammation, [...] Read more.
Natural and sustainable cosmetics represent a rapidly evolving frontier in dermatological science, integrating plant-derived bioactive compounds with advanced delivery technologies and environmentally conscious formulation design. Botanical ingredients, including polyphenols, flavonoids, terpenoids, alkaloids, and polysaccharides, modulate key biological pathways involved in oxidative stress, inflammation, extracellular matrix remodeling, pigmentation, and immune responses, thereby supporting skin regeneration, protection, and homeostasis. To overcome limitations related to instability, compositional variability, and limited skin penetration, these compounds are increasingly incorporated into advanced delivery systems such as nanoemulsions, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), vesicular systems, microneedle platforms, three-dimensional matrices, and plant-derived extracellular vesicles (PDEVs). These technologies enhance cutaneous bioavailability, enable controlled release, and improve tissue targeting, linking formulation design to exposure–response relationships. In parallel, sustainability has become a critical component of product development. Circular economy strategies, including the upcycling of agro-industrial by-products, green extraction technologies, biodegradable packaging, and life cycle assessment, are reshaping cosmetic innovation. Regulatory frameworks are also evolving to address safety, efficacy, and transparency of natural claims, as well as the challenges of botanical standardization. This narrative review, conducted through a structured literature search, provides a mechanistically oriented analysis of botanical ingredients in dermatology, emphasizing molecular pathways, skin delivery science, and safety considerations. Rather than cataloguing ingredients, it proposes a translational framework linking phytochemistry, delivery science, safety-by-design principles, and sustainability to support the rational development of effective and safe dermatological formulations. Full article
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33 pages, 1767 KB  
Review
The Significance of Solid Lipid Nanoparticles (SLNs) and Nanostructured Lipid Carriers (NLCs) in the Treatment of Atopic Dermatitis
by Christophor Lazov, Krassimira Yoncheva and Marta Slavkova
Sci. Pharm. 2026, 94(1), 19; https://doi.org/10.3390/scipharm94010019 - 18 Feb 2026
Viewed by 2112
Abstract
Lipid nanoparticles have been a subject of intense scientific interest in recent years due to their inherent biocompatibility, versatile delivery routes, drug loading and potential large-scale production. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are matrix lipid nanoparticles that differ in [...] Read more.
Lipid nanoparticles have been a subject of intense scientific interest in recent years due to their inherent biocompatibility, versatile delivery routes, drug loading and potential large-scale production. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are matrix lipid nanoparticles that differ in their lipid composition and, specifically, the presence of liquid lipid in the latter. Their production is straightforward and relatively inexpensive. They provide an additional specific advantage for dermal delivery in the treatment of atopic dermatitis, as they can carry various drugs and even ameliorate the skin condition on their own. The chronic character and the observed predominance of atopic dermatitis in the pediatric population further justify the utility of improved therapeutic strategies and the application of SLNs and NLCs specifically. Therefore, in the current review, we aimed to systematically collect the available literature on this topic and to evaluate where we stand in terms of scientific and practical knowledge. The observations show significant potential for clinical translation for both SLNs and NLCs in the near future. However, some key limitations were identified and discussed. The novelty of this review lies in its systematic consolidation and critical discussion of SLNs and NLCs specifically in the context of atopic dermatitis. Full article
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13 pages, 5109 KB  
Article
Biodistribution of Tc-99m-Labeled Solid Lipid Nanoparticles and Evaluation of Their Possibility as a Radiopharmaceutical
by Hayrettin Eroglu, Arif Kürsad Ayan and Ayse Yenilmez
Molecules 2026, 31(4), 654; https://doi.org/10.3390/molecules31040654 - 13 Feb 2026
Cited by 1 | Viewed by 540
Abstract
Solid lipid nanoparticles (SLNs) are submicron colloidal systems widely investigated as drug carriers; however, their intrinsic biodistribution properties are also critical when SLNs are considered for diagnostic imaging. In the present proof-of-concept study, drug-free SLNs were evaluated exclusively as a radiolabeled imaging agent [...] Read more.
Solid lipid nanoparticles (SLNs) are submicron colloidal systems widely investigated as drug carriers; however, their intrinsic biodistribution properties are also critical when SLNs are considered for diagnostic imaging. In the present proof-of-concept study, drug-free SLNs were evaluated exclusively as a radiolabeled imaging agent rather than as a drug delivery system. SLNs were radiolabeled with Technetium-99m (99mTc), and their in vivo biodistribution was investigated using gamma camera imaging, ex vivo organ counting, and confocal microscopy. SLNs were prepared by a microemulsion–low-temperature solidification method and characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC). Radiolabeling efficiency was determined by instant thin-layer chromatography (ITLC) and exceeded 95%. Following intravenous administration in a rabbit model, dynamic scintigraphic imaging demonstrated predominant uptake in the liver and spleen. These findings were quantitatively confirmed by ex vivo biodistribution analysis at 4 h post-injection and qualitatively supported by confocal microscopy of liver and spleen tissues. The results indicate that 99mTc-labeled SLNs behave as RES-targeting radiocolloids and may serve as potential agents for liver–spleen scintigraphy. Full article
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17 pages, 801 KB  
Perspective
Antioxidant Delivery Revisited: The Promise of Nanostructured Lipid Carriers
by Leif Behar and Holly Siddique
Medicines 2026, 13(1), 2; https://doi.org/10.3390/medicines13010002 - 22 Jan 2026
Viewed by 988
Abstract
Natural products have an invaluable therapeutic effect on human health. Natural antioxidants, including beta-carotene, turmeric, and polyphenols, are recognised for their health benefits but face significant barriers related to insufficient solubility, instability, volatility, and diminished bioavailability, which limit their therapeutic efficacy in drug [...] Read more.
Natural products have an invaluable therapeutic effect on human health. Natural antioxidants, including beta-carotene, turmeric, and polyphenols, are recognised for their health benefits but face significant barriers related to insufficient solubility, instability, volatility, and diminished bioavailability, which limit their therapeutic efficacy in drug delivery systems. Therefore, encapsulation of natural products in a carrier addresses the above concern. Drug delivery systems, such as solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), are promising carriers for effective release, consisting of solid and liquid lipids, which enhance efficiency, stability, and controlled release, thereby minimising bioavailability limitations. This review consolidates current studies on the formulation methodologies, mechanisms of action, and therapeutic applications of NLCs, emphasizing their use in the treatment of conditions such as cancer, neurological disorders, and cardiovascular diseases. The results demonstrate that NLCs substantially enhance the bioavailability and therapeutic efficacy of antioxidants, thereby improving their targeted administration and clinical effects. Nonetheless, difficulties in clinical translation remain, including drug loading capacity, regulatory authorisation, and the need for pervasive research on cytotoxicity. This article highlights important areas for future inquiry, specifically the optimisation of NLC formulations, the enhancement of targeting accuracy, and the resolution of safety issues to enhance their clinical application. Full article
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22 pages, 2615 KB  
Article
Comparative Characterization and Evaluation of WS6 Loaded Nanoformulations Using Solid Lipid, PLGA, and PCL Versus Eudragit RS/RL Prepared by Microfluidics
by Marwa Mohammad, Duaa Abuarqoub, Mohammad Alnatour, Abdolelah Jaradat, Nidal A. Qinna, Ghayda’ AlDabet, Alqassem H. Abuarqoub and Abdalla Awidi
Appl. Nano 2026, 7(1), 1; https://doi.org/10.3390/applnano7010001 - 30 Dec 2025
Viewed by 955
Abstract
Objectives: This study aimed to optimize WS6-loaded nanoparticles (NPs) with favorable therapeutic properties, including appropriate size, low toxicity, high encapsulation efficiency, and enhanced biocompatibility, for selective cancer targeting and regenerative applications. Methods: Three formulations were investigated: solid lipid nanoparticles (SLNs), polycaprolactone (PCL)-based NPs, [...] Read more.
Objectives: This study aimed to optimize WS6-loaded nanoparticles (NPs) with favorable therapeutic properties, including appropriate size, low toxicity, high encapsulation efficiency, and enhanced biocompatibility, for selective cancer targeting and regenerative applications. Methods: Three formulations were investigated: solid lipid nanoparticles (SLNs), polycaprolactone (PCL)-based NPs, and Eudragit RS100-based NPs via microfluidic synthesis. Their physicochemical properties were assessed, followed by biological evaluation on normal cells—dental-derived stem cells (DSCs), gingival fibroblasts (GFs), and human dermal fibroblasts (HDFs)—and cancer cell lines MDA-231 and HepG2. Assays included MTT for viability, apoptosis/necrosis, cell cycle analysis, ROS detection, and cytokine profiling. Results: SLNs showed inherent toxicity despite improved viability upon WS6 loading. PCL NPs improved encapsulation and compatibility but lacked stability. The microfluidic RS-WS6 NPs exhibited optimal characteristics, significantly enhancing viability in normal cells and selectively inducing apoptosis in cancer cells. At 1 µM, RS-WS6 NPs reduced ROS in normal cells (p < 0.05) and increased it in cancer cells (p < 0.05). Cytokine analysis revealed significant downregulation of IL-6, IL-12p70, and TNF-α (p < 0.05), indicating immunomodulatory potential. Conclusions: RS-WS6 NPs developed via microfluidics offer a promising therapeutic platform with selective cytotoxicity against cancer cells, minimal toxicity to normal cells, and anti-inflammatory properties, supporting their use in targeted therapy and regenerative medicine. Full article
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19 pages, 6531 KB  
Article
The Toxic Effect and Mechanism of TMZ Combined with siHOXB9 on Glioblastoma Cells
by Xiaoyu Liu, Yunfei Liu, Wenxuan Li, Qianwen Wang, Ziyu Huang, Xiyu Cheng, Qiong Yan and Honggang Hu
Int. J. Mol. Sci. 2026, 27(1), 79; https://doi.org/10.3390/ijms27010079 - 21 Dec 2025
Viewed by 755
Abstract
Glioblastoma (GBM) represents a highly invasive primary malignant tumor within the central nervous system (CNS). Temozolomide (TMZ), a first-line chemotherapy agent for GBM treatment, has significant limitations, including drug resistance, poor water solubility, a short half-life, and notable toxic side effects. The innovation [...] Read more.
Glioblastoma (GBM) represents a highly invasive primary malignant tumor within the central nervous system (CNS). Temozolomide (TMZ), a first-line chemotherapy agent for GBM treatment, has significant limitations, including drug resistance, poor water solubility, a short half-life, and notable toxic side effects. The innovation of the TMZ dosage form is pivotal for enhancing its therapeutic efficacy. In this study, solid lipid nanoparticles (SLN) loaded with Angiopep-2 (A2) and TMZ (TMZ-A2SLN), a nanopolymer featuring a solid spherical morphology and a particle size of approximately 100 nm, were constructed. The combined effect of TMZ-A2SLN and small-interfering RNA (siRNA) that can knock down the expression of the HOXB9 gene (siHOXB9) augmented the sensitivity of the glioma cell line U251 to TMZ. Under the combined effect, the viability of U251 cells was reduced by 77%. Meanwhile, the mortality rate increased by approximately 45%, and the cell apoptosis rate rose by around 36%. The number of cells arrested in the G2/M and S phases rose. Proteomic analysis indicates that TMZ-A2SLN might be implicated in the pro-inflammatory signaling cascade, tumor migration, invasion, and angiogenesis during the treatment of glioma cells. Moreover, HOXB9 may play a crucial regulatory role in the PPAR signaling pathway, the neural signaling pathway, the phospholipase D signaling pathway, the IL-17 signaling pathway, mineral absorption, and other pathways during glioma cell treatment. Full article
(This article belongs to the Section Molecular Neurobiology)
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13 pages, 936 KB  
Article
Diroximel Fumarate-Loaded Solid Lipid Nanoparticles (DRF-SLNs) as Potential Carriers for the Treatment of Multiple Sclerosis: Preformulation Study
by Debora Santonocito, Giuliana Greco, Maria Grazia Sarpietro, Aurélie Schoubben, Claudia Sciacca, Giuseppe Romeo, Katia Mangano and Carmelo Puglia
Int. J. Mol. Sci. 2025, 26(24), 11827; https://doi.org/10.3390/ijms262411827 - 7 Dec 2025
Viewed by 877
Abstract
Diroximel fumarate (DRF) is an orally administered prodrug used in multiple sclerosis (MS) treatment. Although it exhibits better gastrointestinal (GI) tolerability than its analogues, many patients still discontinue therapy due to frequent GI adverse events. To overcome these limitations, alternative drug delivery systems [...] Read more.
Diroximel fumarate (DRF) is an orally administered prodrug used in multiple sclerosis (MS) treatment. Although it exhibits better gastrointestinal (GI) tolerability than its analogues, many patients still discontinue therapy due to frequent GI adverse events. To overcome these limitations, alternative drug delivery systems that bypass the GI tract are needed. Direct nose-to-brain delivery represents a promising approach to circumvent the blood–brain barrier and target the central nervous system; however, limited nasal mucosal absorption and the small volume of the nasal cavity pose significant challenges. Solid lipid nanoparticles (SLNs) can potentially overcome these obstacles by enhancing drug bioavailability and protecting against enzymatic degradation. This research aimed to develop an innovative intranasal nanoformulation of DRF to improve brain targeting and patient compliance. DRF-loaded SLNs were prepared using a solvent-diffusion technique with stearic acid as the lipid phase and Poloxamer 188 as the surfactant. The obtained nanoparticles displayed favorable technological characteristics, with a mean diameter of 210 nm, a polydispersity index of 0.17, and a zeta potential of −36 mV, suggesting good long-term stability. Interactions between SLNs and biomembrane models (MLV) were also studied to elucidate their cellular uptake mechanism. Future work will focus on evaluating the in vivo efficacy of this novel nanoformulation. Full article
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28 pages, 7715 KB  
Article
Functional pH-Responsive Nanoparticles for Immune Reprogramming in MSS Colorectal Cancer via ER Stress-Induced Proteostasis Disruption, PD-L1-Targeting miRNA, and TLR7 Activation
by Yu-Li Lo, Hua-Ching Lin, Ching-Yao Li, Bryant Huang, Ching-Ping Yang, Hui-Yen Chuang and Tsui-Fen Chou
Pharmaceutics 2025, 17(11), 1503; https://doi.org/10.3390/pharmaceutics17111503 - 20 Nov 2025
Cited by 1 | Viewed by 1579
Abstract
Background: Colorectal cancer (CRC), particularly the microsatellite-stable (MSS) subtype, remains largely unresponsive to immune checkpoint inhibitors (ICIs) due to immune escape, tumor-associated macrophage (TAM) enrichment, and cytokine-driven suppression that sustain a TAM-dominant tumor microenvironment (TME). To overcome these barriers, a pH-responsive solid lipid [...] Read more.
Background: Colorectal cancer (CRC), particularly the microsatellite-stable (MSS) subtype, remains largely unresponsive to immune checkpoint inhibitors (ICIs) due to immune escape, tumor-associated macrophage (TAM) enrichment, and cytokine-driven suppression that sustain a TAM-dominant tumor microenvironment (TME). To overcome these barriers, a pH-responsive solid lipid nanoparticle (SLN) system was engineered to co-deliver CB-5083 (a VCP/p97 inhibitor), miR-142 (a PD-L1-targeting microRNA), and imiquimod (R, a TLR7 agonist) for spatially confined induction of endoplasmic reticulum stress (ERS) and immune reprogramming in MSS CRC. Methods: The SLNs were coated with PEG–PGA for pH-triggered de-shielding and functionalized with PD-L1- and EGFR-binding peptides plus an ER-homing peptide, enabling tumor-selective and subcellular targeting. Results: The nanoplatform displayed acid-triggered PEG–PGA detachment, selective CRC/TAM uptake, and ER localization. CB-mediated VCP inhibition activated IRE1α/XBP1s/LC3II, PERK/eIF2α/ATF4/CHOP, and JNK/Beclin signaling, driving apoptosis and autophagy, while miR-142 suppressed PD-L1 expression and epithelial–mesenchymal transition markers. R facilitated dendritic cell maturation and M1 polarization. Combined CB + miR + R/SLN-CSW suppressed IL-17, G-CSF, and CXCL1, increased infiltration of CD4+ and CD8+ T cells, reduced Tregs and M2-TAMs, and inhibited tumor growth in CT-26 bearing mice. The treatment induced immunogenic cell death, reprogramming the TME into a T cell-permissive state and conferring resistance to tumor rechallenge. Biodistribution analysis confirmed tumor-preferential accumulation with minimal off-target exposure, and biosafety profiling demonstrated low systemic toxicity. Conclusions: This TME-responsive nanoplatform therefore integrates ERS induction, checkpoint modulation, and cytokine suppression to overcome immune exclusion in MSS CRC, representing a clinically translatable strategy for chemo-immunotherapy in immune-refractory tumors. Full article
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30 pages, 3516 KB  
Review
Advanced Nanosystems and Emerging Therapies: Innovations in Tuberculosis Treatment and Drug Resistance
by Akhil Sharma, Vikas Sharma, Shivika Sharma, Sonu Sharma, Monu Sharma and Iyyakkannu Sivanesan
Pharmaceutics 2025, 17(11), 1459; https://doi.org/10.3390/pharmaceutics17111459 - 12 Nov 2025
Cited by 5 | Viewed by 2365
Abstract
Tuberculosis (TB) remains a significant worldwide health challenge due to the limitations of conventional treatments and the rising incidence of drug-resistant Mycobacterium tuberculosis strains. This review consolidates the advancements in nanotechnology-based therapeutics, inhalable formulations, CRISPR–Cas tools, host-directed therapies (HDTs), and nanoparticle-based vaccine development [...] Read more.
Tuberculosis (TB) remains a significant worldwide health challenge due to the limitations of conventional treatments and the rising incidence of drug-resistant Mycobacterium tuberculosis strains. This review consolidates the advancements in nanotechnology-based therapeutics, inhalable formulations, CRISPR–Cas tools, host-directed therapies (HDTs), and nanoparticle-based vaccine development aimed at enhancing TB management. Novel nanocarriers such as liposomes, solid-lipid nanoparticles (SLNs), dendrimers, and polymeric nanoparticles (NPs) offer enhanced bioavailability of drugs, sustained release, as well as targeted delivery to infected macrophages, thereby reducing systemic toxicity and dosing frequency. Inhalable nanomedicines provide localized delivery to the pulmonary site, enhancing the concentration of the drug at the primary site of infection. CRISPR–Cas technology is emerging as a transformative approach to disabling drug-resistant genes and enhancing diagnostic precision. HDTs, including agents like vitamin D and metformin, show potential in modulating host immune responses and enhancing pathogen clearance. Nanoparticle-based vaccines, including mRNA and antigen-conjugated platforms, aim to overcome the limitations of the BCG vaccine by enhancing antigen presentation and eliciting stronger, longer-lasting immunity. Collectively, these modalities mark a shift toward more personalized, effective, and less toxic TB therapies. However, challenges such as regulatory approval, safety, scalability, and accessibility remain. This review highlights the integrated potential of nanomedicine, gene editing, and immunomodulation to transform TB care and combat drug resistance, paving the way for more robust and durable treatment strategies. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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33 pages, 1762 KB  
Review
Advances in Oral Drug Delivery Systems for Natural Polyunsaturated Fatty Acids: Enhancing Bioavailability and Therapeutic Potential
by Matheus Felipe Zazula, Roberta Pozzan, Guilherme Anacleto dos Reis, Mônica Maciel, Thomas Horlem, Tayná Nery Banckes, Josilene Lima Serra Pereira, Ceci Sales-Campos, Luiz Claudio Fernandes, Walter José Martinez-Burgos and Katya Naliwaiko
Pharmaceutics 2025, 17(11), 1377; https://doi.org/10.3390/pharmaceutics17111377 - 24 Oct 2025
Cited by 2 | Viewed by 1989
Abstract
Omega-3 and omega-6 fatty acids play essential roles in human health, being widely used in the prevention and treatment of various conditions, such as cardiovascular diseases, inflammation, and metabolic disorders. However, their oral administration faces significant challenges, including low solubility, rapid oxidation, and [...] Read more.
Omega-3 and omega-6 fatty acids play essential roles in human health, being widely used in the prevention and treatment of various conditions, such as cardiovascular diseases, inflammation, and metabolic disorders. However, their oral administration faces significant challenges, including low solubility, rapid oxidation, and low bioavailability, which limit their therapeutic efficacy. This article explores recent advances in oral drug delivery systems designed for polyunsaturated fatty acids, highlighting how innovative technologies, such as nanoemulsions, liposomes, microencapsulation, and solid lipid nanoparticles (SLNs/NLCs), can improve their stability, absorption and clinical performance. In addition, the main natural sources of these compounds, as well as their extraction and purification methods, and the challenges related to their absorption and metabolism are discussed. This narrative review was based mainly on a comprehensive search of peer-reviewed literature published between 2015 and 2025 in PubMed, Scopus, and Web of Science. The therapeutic benefits of these emerging approaches are analyzed by comparing conventional methods with modern delivery strategies to optimize the use of omega-3 and omega-6 in the body. Finally, the article outlines future perspectives and regulatory challenges associated with these technologies, highlighting their potential to revolutionize the administration of essential fatty acids and broaden their applications in medicine and nutrition. Full article
(This article belongs to the Special Issue Drug Delivery for Natural Extract Applications)
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21 pages, 1382 KB  
Article
Formulation and Comparative Characterization of SLNs and NLCs for Targeted Co-Delivery of Paclitaxel and Hydroxytyrosol Carboxylic Acid Esters Against Triple-Negative Breast Cancer
by Elena Peira, Simona Sapino, Daniela Chirio, Fabio Bucciol, Flavia Turku, Emanuela Calcio Gaudino, Giancarlo Cravotto, Chiara Riganti and Marina Gallarate
Pharmaceutics 2025, 17(9), 1208; https://doi.org/10.3390/pharmaceutics17091208 - 16 Sep 2025
Cited by 4 | Viewed by 1202
Abstract
Background: The management of triple-negative breast cancer (TNBC) remains a therapeutic challenge due to the presence of multidrug resistance (MDR) and hypoxia-induced chemoresistance, both of which substantially reduce the efficacy of conventional chemotherapy. Although certain natural compounds have shown the ability to modulate [...] Read more.
Background: The management of triple-negative breast cancer (TNBC) remains a therapeutic challenge due to the presence of multidrug resistance (MDR) and hypoxia-induced chemoresistance, both of which substantially reduce the efficacy of conventional chemotherapy. Although certain natural compounds have shown the ability to modulate these resistance mechanisms, their clinical application is hindered by poor solubility and limited bioavailability. Among such phenolic compounds, 7-hydroxytyrosol (HTyr)—a phenolic compound from olive oil and olive leaves—has been reported to modulate hypoxia-inducible factor-1 (HIF-1). Methods: In this study, we developed hyaluronic acid (HA)-decorated solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) for the targeted and synergistic co-delivery of paclitaxel (PTX) and hydroxytyrosol carboxylic acid esters (Cn-HTyrCA), precursors that share the antioxidant biphenolic moiety with HTyr. Results: Among the formulations tested, SLNs of trilaurin (TL) exhibited the highest entrapment efficiency (EE%), optimal average particle size, Zeta potential, and good colloidal stability. Of the synthesized Cn-HTyrCA derivatives, C8- and C10-HTyrCA showed superior loading capacity. In vitro release profiles indicated a sustained drug release pattern for both nanoparticles. HA decoration led to a marked increase in particle size and induced a shift in surface charge, confirming successful decoration and suggesting enhanced targeting potential via HA-CD44 interaction. Cytotoxicity assays conducted on MDA-MB-231 cells showed that PTX-loaded TL-SLNs exerted enhanced antitumor activity, particularly when HA-decorated, and a synergistic effect was observed upon co-administration with SLNs loaded with C8-HTyrCA. Conclusions: Overall, our findings support the potential of SLN as a promising strategy to overcome key resistance mechanisms in TNBC, enabling reduced chemotherapeutic dosing and improving therapeutic outcomes. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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